Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India.
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India.
Int J Biol Macromol. 2019 Oct 1;138:359-369. doi: 10.1016/j.ijbiomac.2019.07.093. Epub 2019 Jul 16.
Binding of anticancer drug altretamine with bovine serum albumin (BSA) and its inhibitory effect on fibrillation of the protein has been studied by using a combination of spectroscopic and calorimetric methods. Altretamine is observed to bind with BSA with a moderate binding affinity of the order of 10, which is weakly temperature dependent. Circular dichroism, fluorescence spectroscopic and dynamic light scattering methods have been employed to monitor the conformational change in the protein. Time correlated single photon counting measurements have confirmed ground state complexation of the drug with the protein. Docking studies have led to identification of binding sites on BSA at site III in domain IB. Thioflavin T (ThT) fluorescence emission has been used as a tool to monitor the formation of fibrils/aggregates in BSA. It is observed that anticancer drug altretamine can also act as an inhibitor of fibrillation in BSA and hence can be useful in the treatment of neuro-degenerative diseases. Differential scanning calorimetry has been employed to study the thermal transitions of BSA at different stages of the fibrillation process with and without altretamine to obtain insights into the extent of stabilisation provided by the drug to the protein in native, nucleation/elongation and matured state in the fibrillation process.
通过使用光谱和量热法相结合的方法，研究了抗癌药物氨磷汀与牛血清白蛋白（BSA）的结合及其对蛋白质纤化的抑制作用。结果表明，氨磷汀与 BSA 具有中等强度的结合亲和力，约为 10，且这种亲和力对温度的依赖性较弱。圆二色性、荧光光谱和动态光散射方法被用于监测蛋白质的构象变化。时间相关单光子计数测量证实了药物与蛋白质的基态络合。对接研究确定了 BSA 在域 IB 中 III 位点上的结合位点。硫黄素 T（ThT）荧光发射被用作监测 BSA 中纤维/聚集体形成的工具。结果表明，抗癌药物氨磷汀也可以作为 BSA 纤化的抑制剂，因此在治疗神经退行性疾病方面可能有用。差示扫描量热法被用于研究 BSA 在有和没有氨磷汀的情况下，在纤化过程的不同阶段的热转变，以了解药物在纤化过程中对蛋白质的天然、成核/延伸和成熟状态提供的稳定程度。
